Age-related cataracts have been associated with a number of risk factors, including exposure to ultraviolet light, oxidative stress, diabetes, and nutritional deficiencies. The purpose of our research is to use gene discovery technologies to better understand the underlying regulatory mechanisms that play a role in age-related cataract. We have used model systems of cataract and compared expressed gene changes between control and cataract lenses using differential display and DNA microarray analyses. Expressed gene changes were observed in model systems of cataract. For instance, up regulation of alpha smooth muscle actin and down regulation of matrix metalloproteinase was observed when rat lenses were exposed to riboflavin and light, which generates superoxide and hydrogen peroxide. These lenses developed opacities. The change in actin and matrix metalloproteinase suggest possible transdifferentiation and cellular restructuring as has been observed in early stages of cataract. In a second system, we tested the hypothesis that lens cells use antioxidant defense systems to protect against oxidative stress. By differential display and microarray, followed by RT-PCR confirmation, we found that catalase and glutathione perxoidase were up regulated in a lens cell line that has been conditioned to survive in 125 microM hydrogen peroxide. The activities of these enzymes were also up regulated. This confirms our hypothesis that lens cells are capable of using detoxification enzymes as a first line of defense against oxidative stress. In aging, these enzymes decrease and it is believed that a threshold is reached where the lens can no longer defend against oxidative stress from ultraviolet light exposure.